<P>Isorhynchophylline (Rhy) is an active pharmacological component of <I>Uncaria rhynchophylla</I> that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known abo...
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https://www.riss.kr/link?id=A107513726
2017
-
SCOPUS,SCIE
학술저널
1095
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
<P>Isorhynchophylline (Rhy) is an active pharmacological component of <I>Uncaria rhynchophylla</I> that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known abo...
<P>Isorhynchophylline (Rhy) is an active pharmacological component of <I>Uncaria rhynchophylla</I> that has been reported previously to exert significant antihypertensive and neuroprotective effects. However, very little is known about its potential anti-cancer activities. This study was carried out to evaluate the anticancer effects of Rhy against various human carcinoma cell lines. We found that Rhy exhibited substantial cytotoxic effect against human hepatocellular carcinoma HepG2 cells when compared with other human carcinoma cell lines including those of lung, pancreas, prostate, head and neck, breast, multiple myeloma, brain and renal cell carcinoma. Rhy induced apoptosis as characterized by accumulation of cells in sub G1 phase; positive Annexin V binding; activation of caspase-8, -9, and -3; and cleavage of PARP (poly-ADP ribose polymerase). This effect of Rhy correlated with the down-regulation of various proteins that mediated cell proliferation, cell survival, metastasis, and angiogenesis. Moreover, cell proliferation, migration, and constitutive CXCR4 (C-X-C chemokine receptor type 4), MMP-9 (Matrix metallopeptidase-9), and MMP-2 expression were inhibited upon Rhy treatment. We further investigated the effect of Rhy on the oncogenic cell signaling cascades through phospho-kinase array profiling assay. Rhy was found to abrogate phospho-p38, ERK, JNK, CREB, c-Jun, Akt, and STAT3 signals, but interestingly enhanced phospho-p53 signal. Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells.</P>
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